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Do ACE Inhibitors Provide Protection for Diabetics?

Am Fam Physician. 2000 May 15;61(10):3140-3142.

Diabetes greatly increases the risk of cardiovascular disease. Studies have shown that the risk of cardiovascular events is two to three times higher in men with diabetes and three to five times higher in women with diabetes. Seventy percent of deaths in patients with diabetes are related to cardiovascular events. The age-adjusted prevalence of 45 percent in white adults who have diabetes is approximately twice that in comparable patients who do not have diabetes. This alarming disparity is likely to increase despite the fact that the incidence of heart disease is declining in the general population. In patients with diabetes, the incidence of heart disease is not declining but may be stable or rising. Angiotensin-converting enzyme (ACE) inhibitors are known to prevent or delay cardiovascular events and, in patients with diabetes, they also have been shown to be beneficial after acute myocardial infarction, hypertension and microvascular renal disease. The Heart Outcomes Prevention Evaluation (HOPE) study investigated the effectiveness of the ACE inhibitor ramipril in reducing cardiovascular events in adults with diabetes.

Patients were part of the HOPE study cohort, a large multifaceted study of cardiovascular disease in persons 55 years or older with a history of cardiovascular disease. Patients were eligible for this study if they also had diabetes and at least one significant cardiovascular risk factor. Patients were excluded if they had congestive heart failure, uncontrolled hypertension, low ejection fraction or recent myocardial infarction. Following comprehensive assessment and a run-in period, patients who met the study criteria were randomized to receive 10 mg of ramipril daily for seven to 10 days or an identical placebo. Patients were reassessed after one month, and then every six months for more than four years. The end points of the study were development of myocardial infarction, stroke or cardiovascular death. Secondary end points included congestive heart failure, angina and necessity for a cardiovascular revascularization procedure.

At the end of the first year, more than 80 percent of patients were compliant with assigned medications. After four years, compliance was 65 percent. The only notable side effect was a cough, which resulted in 5 percent of the ramipril group dropping out of the study. The rate of cardiovascular death, stroke or myocardial infarction was significantly lower in the ramipril group than in the placebo group. After one year, the risk for a primary outcome in the ramipril group was reduced by 16 percent, and after two years by 26 percent. This reduction was sustained during follow-up. Ramipril reduced the risk of myocardial infarction by 22 percent, stroke by 33 percent and cardiovascular death by 37 percent. In addition, the risk of a revascularization procedure was reduced by 17 percent and the risk of nephropathy by 24 percent. After adjustment for changes in blood pressure, the combined reduction in primary outcomes was 25 percent. The study was stopped early because of the consistent benefits associated with ramipril.

The authors conclude that this study confirms earlier evidence of the potential of ACE inhibitors to prevent cardiovascular disease. These benefits also appear to provide significant protection from microvascular disease in patients with diabetes.

Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. January 22, 2000;355:253–9.


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